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Article

Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression

1
Institute Teofilo Hernando for Drug Discovery, Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, Spain
2
Instituto de Investigación Biosanitaria Hospital de la Princesa, 28006 Madrid, Spain
3
Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA 92697, USA
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(7), 644; https://doi.org/10.3390/antiox9070644
Received: 10 June 2020 / Revised: 13 July 2020 / Accepted: 19 July 2020 / Published: 21 July 2020
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
Neuroinflammation and oxidative stress are being recognized as characteristic hallmarks in many neurodegenerative diseases, especially those that portray proteinopathy, such as Alzheimer’s disease (AD). Heme-oxygenase 1 (HO-1) is an inducible enzyme with antioxidant and anti-inflammatory properties, while microglia are the immune cells in the central nervous system. To elucidate the brain expression profile of microglial HO-1 in aging and AD-progression, we have used the 5xFAD (five familial AD mutations) mouse model of AD and their littermates at different ages (four, eight, 12, and 18 months). Total brain expression of HO-1 was increased with aging and such increase was even higher in 5xFAD animals. In co-localization studies, HO-1 expression was mainly found in microglia vs. other brain cells. The percentage of microglial cells expressing HO-1 and the amount of HO-1 expressed within microglia increased progressively with aging. Furthermore, this upregulation was increased by 2–3-fold in the elder 5xFAD mice. In addition, microglia overexpressing HO-1 was predominately found surrounding beta-amyloid plaques. These results were corroborated using postmortem brain samples from AD patients, where microglial HO-1 was found up-regulated in comparison to brain samples from aged matched non-demented patients. This study demonstrates that microglial HO-1 expression increases with aging and especially with AD progression, highlighting HO-1 as a potential biomarker or therapeutic target for AD. View Full-Text
Keywords: Heme oxygenase-1; microglia; Alzheimer’s disease; beta-amyloid plaques Heme oxygenase-1; microglia; Alzheimer’s disease; beta-amyloid plaques
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MDPI and ACS Style

Fernández-Mendívil, C.; Arreola, M.A.; Hohsfield, L.A.; Green, K.N.; Lopez, M.G. Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression. Antioxidants 2020, 9, 644. https://doi.org/10.3390/antiox9070644

AMA Style

Fernández-Mendívil C, Arreola MA, Hohsfield LA, Green KN, Lopez MG. Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression. Antioxidants. 2020; 9(7):644. https://doi.org/10.3390/antiox9070644

Chicago/Turabian Style

Fernández-Mendívil, Cristina, Miguel A. Arreola, Lindsay A. Hohsfield, Kim N. Green, and Manuela G. Lopez. 2020. "Aging and Progression of Beta-Amyloid Pathology in Alzheimer’s Disease Correlates with Microglial Heme-Oxygenase-1 Overexpression" Antioxidants 9, no. 7: 644. https://doi.org/10.3390/antiox9070644

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